The second decade of life involves phenomenal changes in hormone levels, growth, body habitus, and behavior. It has been axiomatic that these perturbations are connected, but few investigations have been able to address the issue of behavioral causation during human puberty. A central issue is whether increases in hormone levels directly influence the brain with resultant behavioral effects or whether the adolescent's perception of his/her secondary sex characteristics provide the major basis for behavioral change? The crucial experimental method for establishing a causal role for a hormone by removal of the secretory source and then replacing the endocrine material to be studied has not been applied to behavioral investigations during adolescence. The present proposal will attempt to determine the direct influence of sex hormones on the brain by performing sequential behavior testing in more than 50 sex steroid-deficient adolescents between the ages of 11 and 17 before, during, and after they receive therapeutic hormone replacement therapy. Boys and girls with primary or secondary hypogonadism will be given low, intermediate, and higher physiologic dosage amounts of either testosterone or estrogen, alternating with placebo, over 3-month periods, following established regimes. Intramuscular testosterone enanthate will be administered to boys and oral, conjugated estrogens to girls. The low dosage of sex steroids will approximate the normal, early pubertal hormone milieu and will be furnished in a randomized, double-blind, cross-over design. Intermediate levels of androgen and estrogen will approximate the mid-pubertal sex hormone environment, and the high dose will approximate late pubertal amounts of hormone. Over an 18-21 month period the participants will be tested 7 or 8 times in behavioral domains which include cognition, emotions and behavior problems, sexuality and self-perception, and parental perceptions of emotions and behavior problems. Gender-specific data analysis will direct major attention to longitudinal comparisons of changes in behavior assessed during hormone-replete and hormone-depleted periods. Differences between how androgens affect male behavior and estrogens impinge upon female behavior during adolescence also will be examined. The proposed 3-year, longitudinal study has the potential for making a major advance in explaining how sex steroids in varying doses affect behavior during the pubertal period. Such information will be useful in designing intervention strategies for improved health care to adolescents.